Osteoinduction and Osteoconduction with Porous Beta-Tricalcium Phosphate Implanted after Fibular Resection in Humans

Osteoinductive properties of β-TCP remain unknown in humans. It is important to improve the bone grafts which have been the standard treatment for bone defect due to their biocompatibility and bone-healing properties. The purpose of this study was to radiologically clarify the bone forming property of β-TCP by evaluating the replacement of β-TCP by newly formed bone in the defect after fibular resection and to examine the histological features of a β-TCP specimen three months after grafting. Radiographs of 17 patients who underwent β-TCP grafting were evaluated. Osteoinductive and osteoconductive properties were assessed by examining bone formation from the remnant fibula, periosteum, and β-TCP alone. In one case, β-TCP was removed later because of postoperative complications and was evaluated histologically. Twenty two of 34 sites between the remnant fibula and β-TCP had achieved good bone regeneration. Five of 14 sites between the periosteum and β-TCP had achieved good bone regeneration. We found immature but evident bone formation in three cases with no osseous and periosteal sites. Histological analysis revealed bone formation on the outer macropore surface of β-TCP. Some blood vessels formed in the macropores expressed CD31 and CD34, while a few lymphatic vessels expressed CD34 and podoplanin. Thus, the osteoinductive ability of β-TCP alone was demonstrated in humans radiographically for the first time. The histological morphology of β-TCP was demonstrated at an early stage after grafting in humans.

Preparation of Filling Porous Osteoconduction Materials and Its Animal Experiment Study

Titanium rods were processed into implant samples with cavity and groove in which was filled with HAP/β-TCP porous osteoconduction composite materials in order to increase the mechanical stability of the implant in vivo.The phase compositions of the composite was characterized by X-ray diffraction （XRD） and scanning electron microscopy（SEM）.Histological evaluation showed that the biogradable composite could enhanced the ability of new bone formation.The composite can conduct new bone tissue growing into the cavities gradually after implanted into animal,and then achieve mechanical fixation.The filling biogradable compound exhibited excellent biocompatibility,which combined with the new bone tissues tightly without inflammation and loosing.

Powder metallurgical Ti-Mg metal-metal composites facilitate osteoconduction and osseointegration for orthopedic application

In this work,TieMg metal-metal composites(MMCs)were successfully fabricated by spark plasma sintering(SPS).In vitro,the proliferation and differentiation of SaOS-2 cells in response to TieMg metal-metal composites(MMCs)were investigated.In vivo,a rat model with femur condyle defect was employed,and TieMg MMCs implants were embedded into the femur condyles.Results showed that TieMg MMCs exhibited enhanced cytocompatibility to SaOS-2 cells than pure Ti.The micro-computed tomography(Micro-CT)results showed that the volume of bone trabecula was significantly more abundant around TieMg implants than around Ti implants,indicating that more active new-bone formed around TieMg MMCs implants.Hematoxylin-eosin(H&E)staining analysis revealed significantly greater osteointegration around TieMg implants than that around Ti implants.

Biofunctionalized composite scaffold to potentiate osteoconduction,angiogenesis,and favorable metabolic microenvironment for osteonecrosis therapy

Osteonecrosis is a common orthopedic disease in clinic,resulting in joint collapse if no appropriate treatment is performed in time.Core decompression is a general treatment modality for early osteonecrosis.However,effective bone regeneration in the necrotic area is still a significant challenge.This study developed a biofunctionalized composite scaffold(PLGA/nHA30VEGF)for osteonecrosis therapy through potentiation of osteoconduction,angiogenesis,and a favorable metabolic microenvironment.The composite scaffold had a porosity of 87.7%and compressive strength of 8.9 MPa.PLGA/nHA30VEGF had an average pore size of 227.6μm and a water contact angle of 56.5◦with a sustained release profile of vascular endothelial growth factor(VEGF).After the implantation of PLGA/nHA30VEGF,various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment.Additionally,the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis.The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.

Biological analysis of an innovative biodegradable antibiotic eluting bioactive glass/gypsum composite bone cement for treating experimental chronic MRSA osteomyelitis

A multi-barrier antibiotics loaded biodegradable composite bone cement for resolving chronic osteomyelitis has been studied to understand the physico-mechanical properties,drug loading/eluting efficiency,and different merits and demerits prior to clinical application.After successful induction of bone infection in 28 rabbits using methicillin-resistant Staphylococcus aureus(MRSA)strains,calcium sulfate/bioactive glass based composite cement was implanted in 12 defects to assess its performance over parenteral therapy with microscopic and radiological examination for 90 days.The composite cement revealed acceptable physico-mechanical properties and controlled drug elution kinetics.Furthermore,the antibiotics concentrations in bone up to 42 days were sufficient to kill MRSA without eliciting adverse drug reactions.The striking feature of platelets aggregation by composite cement could assist bone healing.The controlled degradation with simultaneous entrapment of composite cement within the osteoid tissues and complete repair of infected cortical defects(holes)in rabbit tibia at 6 weeks indicated the excellent anti-infective and osteoconductive properties of composite cement.Thus,the animal study demonstrated the superiority of composite over injectable antibiotic therapy based on infection resolution and bone regeneration.We thereby conclude that the composite cement can be effectively applied in the treatment of resistant cases of chronic osteomyelitis.

LONG-TERM OBSERVATION FOR OSSEOINTEGRATION OF CALCIUM PHOSPHATE SOL-GEL COATING ON Ti-6Al-4V IMPLANTS

Objective To observe the long-term impact of calcium phosphate （CaP） sol-gel coating on bone growth around porous-surfaced implant. Methods The porous-surfaced Ti-6Al-4V implants were prepared with the addition of a thin film of CaP sol-gel coating, and implanted into the tibiae of 8 rabbits, each with two implants. Implanted sites were allowed to heal for 2, 8, 12, and 24 weeks, after which specimens were obtained for scanning electron microscope analysis using the freezefracture technique. Results The sol-gel coated implants recovered by freeze-fracture technique showed extensive bone growth from the endosteum along the implant surface. The bone was in direct contact with the CaP layer. The cement line-like layer was clearly demonslxated to be an intervening electron dense afibrillar layer between the CaP coat and the overlying newly deposited bone. The stability and osseointegration of the porous-surfaced implants seemed not to be affected by the osteoclastic resorption of CaP layer occurred during 24 weeks of healing. Conclusion Based on the findings in the long-term observation, the addition of a thin layer of CaP promotes an extensive osseointegrated interface between the porous-surfaced Ti-6Al-4V implants and the newly deposited bone.

Bovine Calcined Bone for the Repair of Radial Defect in a Rabbit Model

In order to investigate the bovine calcined bone's ability of repairing segmental bone defect and seek a new artificial bone substitute material, the bovine calcined bone (450℃,32 h) was implanted into the 10 mm middle radial defect of rabbits with tricalcium phosphate ceramics as the control. By using the methods of histology, radiology and biomechanics their osteogenic ability were measured. It was found that the bovine calcined bone's ability of repairing bone defect was better than that of tricalcium phosphate ceramics. The histological Nilsson′s scores at 3rd, 5th, 9th week after operation were significantly increased ( P <0.01). At 12th week after operation the bending strength of radius in experimental group was much higher than that of control group and turned normal. It was suggested that bovine calcined bone is an ideal artificial bone substitute material with good ability of repairing segmental bone defect and some degree of mechanical strength.

Osteoconductivity of Hydrophilic Surfaces of Zr-9Nb-3Sn Alloy with Hydrothermal Treatment

Zirconium and its alloys are more suitable materials for implant surgery to be performed in a magnetic resonance imaging scanner compared with other implant materials. Although they have high anticorrosion properties in the body, as do titanium and its alloys, they have little use as implants in contact with bone because of their low osteoconductivity (bone-implant contact ratio). To improve the osteoconductivity of zirconium, niobium, and Zr-9Nb-3Sn alloy, we applied a single- step hydrothermal surface treatment using distilled water at a temperature of 180°C for 3 h. The hydrothermally treated samples were stored in a ×5 phosphate-buffered saline (PBS(-)) solution to keep or to improve the water contact angle (WCA), which has a strongly positive effect on osteoconductivity. The specimen surfaces were characterized using scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, surface roughness, and contact angle measurement using a 2 μL droplet of distilled water. The relationship between WCA and osteoconductivity for various surface modifications was examined using in vivo tests. The results showed that a superhydrophilic surface with a WCA ≤ 10° and a high osteoconductivity of up to 40% in cortical bone, about four times higher than the as-polished Zr-9Nb-3Sn and its pure alloy elements, was provided by the combination of hydrothermal surface treatment and storage in ×5 PBS(-).

Copper as an alternative antimicrobial coating for implants-An in vitro study

AIM To investigate osteoconductive and antimicrobial properties of a titanium-copper-nitride(TiC uN) film and an additional BONIT~? coating on titanium substrates.METHODS For micro-structuring, the surface of titanium test samples was modified by titanium plasma spray(TPS). On the TPS-coated samples, the Ti Cu N layer was deposited by physical vapor deposition. The BONIT~? layer was coated electrochemically. The concentration of copper ions released from TiC uN films was measured by atomic absorption spectrometry. MG-63 osteoblasts on Ti Cu N and BONIT~? were analyzed for cell adhesion, viability and spreading. In parallel, Staphylococcus epidermidis(S. epidermidis) were cultivated on the samples and planktonic and biofilm-bound bacteria were quantified bycounting of the colony-forming units. RESULTS Field emission scanning electron microscopy(FESEM) revealed rough surfaces for TPS and TiC uN and a special crystalline surface structure on TiC uN + BONIT~?. TiC uN released high amounts of copper quickly within 24 h. These release dynamics were accompanied by complete growth inhibition of bacteria and after 2 d, no planktonic or adherent S. epidermidis were found on these samples. On the other hand viability of MG-63 cells was impaired during direct cultivation on the samples within 24 h. However, high cell colonization could be found after a 24 h pre-incubation step in cell culture medium simulating the in vivo dynamics closer. On pre-incubated TiC uN, the osteoblasts span the ridges and demonstrate a flattened, well-spread phenotype. The additional BONIT~?-coating reduced the copper release of the TiC uN layer significantly and showed a positive effect on the initial cell adhesion.CONCLUSION The Ti Cu N-coating inhibits the formation of bacterial biofilms on orthopedic implants by influencing the "race for the surface" to the advantage of osteoblasts.

High Osteoconductive Surface of Pure Titanium by Hydrothermal Treatment

Surface properties of Ti implants (especially surface hydrophilicity) influence biological responses at the interface between the bone tissue and the implant. However, only a little research reported the effect of surface hydrophilicity on osteoconductivity by in vivo test. We have investigated the surface characteristics and osteoconductivity of titanium implant produced by hydrothermal treatment using distilled water at temperature of 180°C for 3 h, and compared with as-polished and those of implants produced by anodizing in 0.1 M H2SO4 with applied voltage from 0 V to 100 V at 0.1 Vsˉ1 and anodizing followed by hydrothermal treatment. The relationship between hydrophilic surface and osteoconductivity in various surface modifications was examined by in vivo test. In order to maintain the hydrophilicity of the hydrothermal sample surface, it was kept in to the phosphate buffered saline solution (PBS) with 5 times concentration: 5PBS(-) in room temperature. The surface characteristics were evaluated by scanning electron microscopy, XRD, X-ray photoelectron spectroscopy, surface roughness and contact angle measurement using a 2 μL droplet of distilled water. In in vivo testing, the rod samples (Φ2 × 5 mm) were implanted in male rat’s tibiae for 14 days and the bone-implant contact ratio, RB-I, was used to evaluate the osteoconductivity in the cortical and cancellous bone parts, respectively. As a result, hydrothermal treatment without anodizing still produced a smooth surface like an initial surface roughness of as-polished samples, Ra/μm B-I = 50% in cortical bone part (about four times higher than as-polished Ti) were provided by only hydrothermal process without anodizing after immersing into 5PBS(-).

Osteoconductivity of Superhydrophilic Anodized TiO₂Coatings on Ti Treated with Hydrothermal Processes

Surface hydrophilicity is considered to have a strong influence on the biological reactions of bone-substituting materials. However, the influence of a hydrophilic surface on osteoconductivity is not completely clear, especially for superhydrophilic surfaces. In this study, we conferred superhydrophilic properties on anodized TiO2 coatings using a hydrothermal treatment, and developed a method to maintain this surface until implantation. The osteoconductivity of these coatings was evaluated with in vivo tests. A hydrothermal treatment made the surface of as-anodized samples more hydrophilic, up to a water contact angle of 13 (deg.). Storage in both air and distilled water increased the water contact angle after several days because of the adsorption of hydrocarbon. However, storage in phosphate buffered solution led to a reduction in the water contact angle, because of the adsorption of the inorganic ions in the solution, and the sample retained its high hydrophilicity for a long time. As the water contact angle decreased, the hard tissue formation ratio increased continuously up to 58%, which was about four times higher than the hard tissue formation ratio on as-polished Ti.

Osteoconductivity Control Based on the Chemical Properties of the Implant Surface

Metallic materials, such as Ti, Zr, Nb, Ta, and their alloys, and also stainless steels are widely attractive as osteoconductive materials in the dental and orthopedic fields. Ceramics and polymers are also commonly used as biomaterials. However, they do not have high osteoconductivity in their pure form, and surface coatings with bioactive substances, such as hydroxyapatite or TiO2, are needed before implantation into the bone. Many reports claim that the surface chemical properties of implants, in particular, hydrophilicity and hydrophobicity, strongly affect the biological reactions. However, the effect of surface properties on osteoconductivity is not clear. In this review, we focus on the relationship between the surface hydrophilicity of metallic implants and osteoconductivity using in vivo evaluation, and the control of the osteoconductivity is discussed from the viewpoint of protein adsorption in implants.

Surface Modification of PEEK and Its Osteoconductivity and Anti-Inflammatory Properties

Polyetheretherketone (PEEK) is known as one of the “super-engineering plastics” and is used as an intervertebral disk spacer in the body. PEEK has a hydrophobic surface (water contact angle (WCA) > 80°) and high chemical resistance, and it is thus difficult to perform any surface treatment, such as hydrophilization. In this study, we aimed to form a hydrophilic surface on PEEK without coating layers by using hydroprocessing (aqueous solution processing), and we examined the osteoconductivity and anti-inflammatory properties of surface-treated PEEK in vivo compared with Ti implants. The WCA value of PEEK reached ~20° using a combination of immersion in a solution of >16.2 M H2SO4 and ultraviolet irradiation (172 nm). In in vivo testing, the hydrophilization of PEEK by surface modification without a coating layer improved the osteoconductivity and anti-inflammatory properties. The relationship between the bone-implant contact ratio and the WCA values of the surface-modified PEEK agreed well with that of the surface-treated Ti.

Influence of Alloy Elements on the Osteoconductivity of Anodized Ti-29Nb-13Ta-4.6Zr Alloy

Anodizing is expected to be an effective method to improve the osteoconductivity of the Ti-29Nb-13Ta-4.6Zr (TNTZ) alloy because the bioactivity of anodized Ti is good. However, it is not known how the alloy elements influence the surface roughness, composition, hydrophilicity, and osteoconductivity of the anodized film on the Ti alloy. In this study, we investigated the effects of anodizing on the surface properties and the osteoconductivity of the anodized TNTZ alloy, focusing on the functions of the individual alloy elements. The anodized oxides of the Nb, Ta, and Zr metals were hydrophobic at all the voltages applied, in contrast to the anodized oxide of Ti. As well as pure Ti, a TiO2-based oxide film formed on TNTZ after anodizing. However, the oxide film also contained large amounts of Nb species and the molar Nb/Ti ratio in the TNTZ alloy was high, which makes the surface more hydrophobic than the anodized oxide on Ti. In vivo tests showed that the osteoconductivity of the TNTZ alloy was sensitive to both its surface roughness and hydrophilicity. When the TNTZ alloy was anodized, the process increased either the surface hydrophobicity or the surface roughness at the voltage used in this study. These changes in the surface properties did not improve its osteoconductivity.

Advances in magnesium-containing bioceramics for bone repair

Reconstruction of bone defects or fractures caused by ageing,trauma and tumour resection is still a great challenge in clinical treatment.Although autologous bone graft is considered as gold standard,the source of natural bone is limited.In recent years,regenerative therapy based on bioactive materials has been proposed for bone reconstruction.Specially,numerous studies have indicated that bioactive ceramics including silicate and phosphate bioceramics exhibit excellent osteoinductivity and osteoconductivity,further promote bone regeneration.In addition,magnesium(Mg)element,as an indispensable mineral element,plays a vital role in promoting bone mineralisation and formation.In this review,different types of Mg-containing bioceramics including Mg-containing calcium phosphate-based bioceramics(such as Mg-hydroxyapatite,Mg-biphasic calcium phosphate),Mg-containing calcium silicate-based bioceramics(such as Mg2SiO4,Ca2MgSi2O7 and Mg-doped bioglass),Mg-based biocements,Mg-containing metal/polymer-bioceramic composites were systematacially summarised.Additionally,the fabrication technologies and their materiobiological effects were deeply discussed.Clinical applications and perspectives of magnesium-containing bioceramics for bone repair are highlighted.Overall,Mg-containing bioceramics are regarded as regenerative therapy with their optimised performance.Furthermore,more in-depth two-way researches on their performance and structure are essential to satisfy their clinical needs.